The bone diseases (e.g. bone fractures) can occur in all classes of people due to various causes of sports and traffic accidents. And, since it usually takes a long time to heal them, the bone diseases bring significantly hamperings to the patient's normal daily life. In recent years, the number of osteoporosis patients has increased with the aging of population. So, an incidence of limb bone fractures associated with osteoporosis has markedly increased in proportion to it. Femoral neck bone fracture, in particular, necessitates long-term hospitalization and often brings about internal complications including dementia caused by long-term hospitalization, and pose major social and economic problems. It is an urgent task to allow bone fracture patients to be early discharged from the hospital.
Bone fracture healing is a form of wound healing characterized by local occurrence and progression. Usually, various local factors function well at the site of fracture to promote the healing in vivo. Such factors include peptide-type bioactive substances such as bone morphogenetic proteins (BMPs) and transforming growth factors (TGFs), which have been reported to promote osteogenesis in animal models "Proceedings of the National Academy of Sciences, USA, vol. 87, pp. 2220-2224 (1990), and Endocrinology, vol. 124, pp. 2991-2993 (1989)".
With regard to non-peptide osteogenic promoting substance, for example, prostaglandin A.sub.1 derivatives, vitamin D.sub.3 derivatives, benzylphosphonic acid derivatives, phenolsulfophthalenic acid derivatives have been reported.
The above-mentioned peptide-type bioactive substances are peptides or proteins exceeding 5,000 in molecular weight, and are rapidly metabolized in vivo and lacking stability. With this in mind, some preparations have been produced in an attempt to obtain satisfactory stability, but all failed to achieve sufficient osteogenic promoting activity, and there are no preparations satisfactory as to quality etc. "Clinical Orthopaedics and Related Research, vol. 278, pp. 274-285". Also, the above-mentioned non-peptide osteogenic promoting substance are not clinically effective in terms of osteogenic promoting activity for bone fracture healing.
For these reasons, there is strong demand for a high-quality agent for treating bone disease that is highly stable, safe and active, and that is clinically effective in long-term treatment of bone fractures.